Cold Spring Harbor Laboratory Conference on The PARP Family and Friends: Gene Regulation and Beyond April 9 - 12, 2014 Project Summary This proposal seeks support for the meeting on The PARP Family and Friends: Gene Regulation and Beyond to be held at Cold Spring Harbor Laboratory on April 9 - 12, 2014. The meeting will assemble leaders in the field, together with junior faculty, postdoctoral fellows and graduate students, to present, review, and discuss current research on PARP family members and associated proteins that impact NAD+ signaling and nuclear functions, especially as they pertain to the regulation of gene expression. Recent studies have highlighted the diverse and important roles of ADP-ribosylation reactions in cellular functions, which are catalyzed by a family of mono- and polyADP-ribosyltransferase enzymes (the PARP family). PARP proteins possess an intrinsic enzymatic activity that catalyzes the transfer of ADP-ribose (ADPR) units from nicotinamide adenine dinucleotide (NAD+) onto target proteins, thereby modulating their activities. PARP-1, the founding member of the PARP family, is an abundant nuclear protein that plays key roles in a variety of nuclear processes, including the regulation of transcription. PARP-1 may connect cellular metabolic state, through NAD+, to the control of nuclear functions and ultimately a broad range of physiological and pathophysiological processes, including metabolism, hormone signaling, gene regulation, circadian rhythms, inflammation, and the maintenance of genome integrity. The functions of other PARP family members are less well understood, but recent studies have begun to identify new and exciting roles that suggest tremendous biological diversity for this family. In addition, a growing repertoire of ADPR-binding proteins connects PARP activity to key molecular and cellular processes. Finally, recent progress targeting PARPs with small molecule chemical inhibitors, some of which may alter PARP-1-dependent gene regulatory programs, has shown some promise as a therapeutic approach. The meeting will cover a broad spectrum of topics ranging from the role of PARP family members and ADP-ribosylation in gene regulation, chromatin structure and function, and cellular signaling. In addition, the contribution of PARPs to physiological and pathophysiological states will be covered, including metabolic disorders and cancers. Finally, the molecular actions and potential therapeutic effects of PARP inhibitors will be discussed. Each session will be chaired by a leading scientist in the field. Oral presentations will be given by a group of distinguished invited speakers, as well as speakers selected from submitted abstracts. Selected speakers will include graduate students, postdoctoral fellows and junior faculty aiming for maximal inclusion of young investigators. Of special importance is the a poster session, where many participants can present their work in an atmosphere conducive to informal discussions. The meeting will be of moderate size, and we expect about 200 people to attend, the vast majority of whom will be presenting a poster or talk.